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Laboratory diagnostics of micrometastases in breast cancer patients
Mikulová, Veronika ; Zima, Tomáš (advisor) ; Svoboda, Marek (referee) ; Průša, Richard (referee)
Introduction: The presence of circulating tumor cells (CTC) in the peripheral blood has been associated with worse prognosis and early relapse in breast cancer patients. CTC determination in the peripheral blood has been considered as a liquid biopsy. The aim of this project was to analyze the presence of CTC followed by their molecular characterization with the potential use not only as a new biomarker for real-time monitoring of therapy efficacy but also as a suitable tool for patient's stratification and individualization of treatment for breast cancer. Methods: A total of 54 patients with diagnosed early breast cancer were enrolled into a prospective study. Ten millilitres of peripheral blood were sequentially collected to test for the presence and characterization of CTC during the follow-up of patients. CTC isolation and detection was performed by AdnaTest BreastCancer™ (AdnaGen AG, Germany), which is based on the detection of EpCAM, HER2 and MUC1 specific transcripts in enriched CTC- lysates. cDNA from isolated CTC has been further used for newly optimized qPCR assays for breast tumor and therapy resistance associated genes: TOP1, TOP2A, CSTD, ST6GAL, KRT19 and reference gene actin. qPCR results have been analyzed by Genex software (MultiD Analysis). Results: 195 blood samples have been...
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Using proteomics for screening of potential breast cancer biomarkers
Garcia N Dua, Felicita ; Ing.Anna Kubesová, Ph.D. (referee) ; Flodrová, Dana (advisor)
Breast cancer is one of the most common malignant cancers and the prognosis is closely related to the stage of carcinogenesis process in which it was captured. Lately, attention was focused on the research of new compounds that would reduce the negative impacts of chemotherapy. It was found that retinoids are effective compounds in the fight against cancer. Retinoids have the ability to inhibit tumors of the mammary gland in an early stage of disease. This work deals with the proteomic studies of breast cancer cells and comparing the proteins contained in the cancer cells which were subjected to retinoid therapy. The differences in protein composition were investigated using gel electrophoresis, reversed phase and size exclusion liquid chromatography. The identification and characterization of selected proteins was carried out by MALDI-TOF MS. The use of two-dimensional gel electrophoresis led to the identification of molecular chaperons, which are considered to be important biomarkers not only of breast cancer.
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Primary and secondary prevention of breast cancer in women
WEISSOVÁ, Veronika
Breast cancer is the most common form of cancer in female population in the Czech Republic. In 2002 the Czech Republic joined most European countries and launched nation-wide mammography screening, enabling women to attend regular preventive examinations when they reach 45 years of age. In January 2014 they started to address women to invite them for preventive breast cancer examinations, as part of a nationwide information campaign. Mortality of this cancer has been decreasing in recent years, which can be explained by the increasing quality of treatment and earlier detection of the disease. Therefore, knowledge of primary and secondary prevention is very important. The theoretical part briefly describes the anatomy of female breasts, defines a malignant tumor, as well as epidemiological aspects of breast cancer. Another chapter is about prevention itself. In the secondary prevention I describe self-examination of breasts and the history and nature of mammography screening. I also present organizations implementing preventive programs aimed at breast cancer. The practical part includes research results, which were obtained through quantitative research questionnaires. The research group consisted of women who live in the Ústí region. The questionnaire consisted of 27 questions and was answered by a group of 150 women between 18 and 44 years old and 150 women over 45 years. I handed out these questionnaires in Ústí healthcare center and I also created an electronic questionnaire which I sent across social networks. Out of the 150 (100 %) questionnaires distributed in Ústí healthcare center, I got only 60 back and 58 of them were sufficiently completed for the needs of the research, the return was only 38.7 %. I received the remaining 242 questionnaires electronically. The aim of the study was to explore the awareness of risk factors of breast cancer of women in the Ústí Region and also to find out whether women in the Ústí region carried out self-examination of breasts and if women over 45 attended regular mammography screening. Based on my research aim I set out four hypotheses. Hypothesis 1: Women in the Ústí region are informed about the risk factors of breast cancer. Hypothesis 2: Women at the age of 18 to 44 in the Usti region are more informed about the risk factors of breast cancer than women in the age group over 45. Hypothesis 3: The difference in the frequency of breast self-examination among women in the age group 18 to 44 is statistically more significant than in women in the over 45 age group. Hypothesis 4: Attending mammography examination of women over 45 in the Ústí region rises according to their level of education. The results of testing my hypotheses show that women in the Ústí region are not informed about the risk factors of breast cancer. I assumed that awareness is higher among women in the 18 to 44 age group, but even this hypothesis wasn't proven. Awareness of risk factors is on the same level in category of 18 to 44 years as in women over 45 years of age. Regarding breast self-examination, women in the above 45 years old age group carry out self-examination more often than women 18 to 44 years old. Even the last hypothesis was not confirmed, attendance of mammography doesn't appear to depend on the education of women. Awareness of women needs to increase, especially in case of risk factors of breast cancer. Awareness increase could be achieved by greater information campaign on television, in newspapers, in businesses with high numbers of working women, or in secondary and higher education through various public lectures. Over 90% of women attend Mammography screening according to my research, which are laudable results. The fact that the actual self-examination of breasts isn't carried out at all by more than half of the women in the age group 18 to 44 is serious. This work could serve as teaching or study material to improve general knowledge of this topic.
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Search for new biomarkers for screening and early diagnosis of cancer
KALČÍKOVÁ, Kateřina
Thesis on the topic "Search of New biomakers suitable for screening and early diagnostics of cancer" is dedicated to the issue of cancer, a cancer of the breast, prostate, ovarian and after the new findings out as melanom determination of tumor markers and their implications for clinical practice. Their aim is skouted up biomaker suitable for screening and early diagnostics of carcinoma( cancer ) of the breast, ovarian, prostate and malignant melanoma with utilization of various kinds of immunoassay. The theoretical part gives a brief and comprehensive overview of the epidemiology of selected tumors and tumor markers used and their qualities. In the methodological part are given principles applied iminoanalytics methods a list of the statistical methods and a detailed description of the groups of patients. Results section contains tables with results of biomarkers diveded by sort of avalueted tumors. In the discussion are then analyzed facts that follow from the results. It discussed the process and actualy status of searching convenients biomekers and their combinations that can distinguish a population of benign tumors of the population with malignant tumors and markers which are able to distinguish healthy population from the population with malignant tumors of the breast, ovary, prostate and melanoma. This work may serve as a source of knowledge and results to continue in search of such marker that could be used for screening and early diagnosis of cancer and so to improve the prevention of these illneses in the population.
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Alternative methods of therapy for oncology patients
BĚLOHLAVÁ, Nikola
Breast carcinoma or breast cancer is one of women?s most often diagnosed tumors in the Czech republic. Several types of scientific treatment are currently available nevertheless it is a very serious disease. It is understandable that women suffering from breast cancer and all cancer patients and their relatives expend considerable effort to obtain information about all types of available treatments which can reverse the unfavorable diagnosis. Very often they resort to some form of alternative therapy. Alternative medicine provides a large choice of methods. But the problem is, that positive effects of alternative therapies are not checked (14). Oncological diseases are very serious, therefore alternative therapies pose a risk to oncology patients when they replace scientific treatments as an alternative. The aim of this thesis is to determine the opinion of women with breast cancer on alternative therapies. The component aims of this work are to find out what the women know about the risks and types of alternative therapy methods in oncology, how women?s point of view on this kind of therapy changes, how these methods affected their life and which of this methods are the most popular with women with breast carcinoma. I deal with the biological and psychosocial aspects of breast cancer in the theoretical part of this thesis and then classical and alternative therapies of treatment which can be used during the treatment. The question of the disease of breast cancer is a very individual sphere. It is assumed that information of intimate character will be used. I considered it suitable for this purpose to use a qualitative form of research. I chose the technique of semi-structured interviews. I prepared a list of instructive questions and then added additional questions as required. The respondants to the interviews I recruited using the technique snowball. I found the contacts through a woman who I know very well. The interviews with the women were processed in the form of case studies, I prepared 7 case studies. 11 women were asked but 4 women refused to participate. I divided the women into 3 categories according to their opinion of the alternative therapies of treatment for their disease. Common factor was that non of the women t disturbed or neglected the prescribed plan of treatment provided by a team of specialists. Two of the women momentarily wanted to finish the classical prescribed treatment. The largest part of respondents was favorably inclined toward the alternative methods of treatment. Two women stated that they are sure that the alternative methods were successful. Two respondents said that they have a positive opinion on this treatment, but they are not sure of the positive effect of alternative therapies. Three other respondents had the opposite opinion on the alternative therapies in oncology. One of these women said that her bad opinion of alternative therapies was caused the terrible experience her friend had with alternative medicine. Almost all respondents used one of the alternative methods during their disease despite the fact that most women do not believe in the positive effects. Two women were not aware of the use of any kind of this therapy. The most commonly used methods were food supplements. The minority part of women (2) used biotronics, homeopathy and acupuncture.
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Radiotherapy of breast cancer
TRAKALOVÁ, Barbora
Diagnosis code C50 represents malignant neoplasm of breast. It is the most frequent tumour disease in women. In 2009, 5975 cases were newly diagnosed in women in the Czech Republic and 1607 women died of this disease. There exist many risk factors which can cause tumour such as hereditary disposition, age, menses, menopause and other factors. At the same time, we can influence many factors and so prevent the disease. Prevention is also important, whether in the form of self - investigation of breast or mammography screening, which is recoverable by insurance from the age of 45. Treatment of breast carcinoma includes a lot of medical modalities such as surgical, hormonal and biological treatment, chemotherapy and radiotherapy. This thesis deals in more details with radiotherapy which is irreplaceable in treatment of this disease. Radiotherapy is a treatment of malignant and benign tumours by means of ionising radiation. In order to treat patients with radiotherapy, a team of doctors and radiologists shall create an individual radiation plan for them including the exact target volume, critical organs, radiation technology, fractionation and particular radiation exposure, radiation position and many other data necessary to accurate irradiation. A technology of two tangential fields is the most applied technology at breast cancer treatment. This technology is also applied in Nemocnice České Budějovice a.s. where I have created a file of 60 patients with breast carcinoma treated on oncology department in the year 2011. There have been used 536 verification images on the whole, it means 1608 evaluation. In course of treatment a patient should have an identical radiation position, which is reached with irradiation and fixation aids. However, from various reasons small or bigger deviations from the optimal position happen and therefore a possibility of irradiation of another volume than the required target one can occur. It is necessary to be aware of the fact that during a treatment of oncology patients there can often appear change of weight, change of body shape of a patient and at advanced stages even also change of physical state and movability of a patient. Therefore large deviations can happen in patients with breast carcinoma namely for example in case of breast deformation or abnormal loss of weight due to the treatment. In Nemocnice České Budějovice a.s., the maximum allowed deviation for vertical, lateral and longitudinal axis is stated 0,7 cm and for rotation 3°. I have noticed the acquired deviation values from verification images into a chart and consequently into a figure where are shown the average deviations and frequencies of these deviation in particular axes for each radiation field. The biggest deviation has happened in vertical axis and the average deviation in that axis was 0,29 cm. The maximum allowed deviation was exceeded only at 3 %, so at 45 deviation from the total evaluation. This thesis should prove the fact that verification images enable to prevent possible errors during radiotherapy. This hypothesis has been confirmed because only 3 % evaluation exceeded the maximum allowed deviations. Verification images enable us to disclose wrong irradiation position, therefore only the target volume is irradiated and follows no irradiation of the surrounding healthy tissue and critical organs.
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Secondary tumors after irradiation for carcinoma of the breast
SUKOVÁ, Denisa
One of the most common cancers in women is breast cancer. The incidence of breast cancer is great and its incidence increases after 50 years of age. In 2009, 5,975 women were newly diagnosed. Despite the fact that the treatment of breast cancer, especially in its early stages, is very successful, breast cancer still remains the leading cause of cancer death in women. In 2009, 1,607 women succumbed to this pestilential disease. The main treatment modality is surgical treatment. Breast cancer is moderately chemosensitive and radiosensitive, which suggests a potential treatment using chemotherapy and radiotherapy. Other treatment modalities include hormonal and biological therapies. Radiotherapy is a medical discipline that uses ionizing radiation to treat malignant as well as benign diseases. When applying ionizing radiation, tolerance doses of organs and tissues must be observed. As a result of exceeding the tolerance doses, significant changes and complications reducing the quality of life arise. Because the survival rate of cancer patients is increasing, the study of late effects of cancer treatment is becoming more important. One of the serious late side effects is the formation of secondary tumour. The practical part of the thesis focuses on the issues of radiation-induced tumours in women who have been treated with radiotherapy for breast cancer. The research group consists of patients who were exposed to radiation at a hospital in České Budějovice between 2000 and 2004. The entire group included 516 patients who were exposed to radiation aimed to the breast or chest wall. I monitored in these patients the eventual formation of a duplicate tumour, its location, type, and latency time. I also focused on the calculation of relative risk. After the completion of radiation therapy, a secondary tumour formed in 32 patients, i.e. 6.2 %. Two new tumours were found in one of the patients, the total of 33 secondary tumours was diagnosed. The most frequent types of newly formed tumours were cancers of contralateral breast and non-melanoma skin cancers (basal cell epithelioma). Both tumour types were represented in the number of seven. Furthermore, six lung tumours, three rectal tumours, and two cases of cervical, kidney and bladder tumours were found. In addition, a duplicate tumour of the brain and the meninx, a myeloma, a thyroid tumour, and an endometrial tumour were found. 58 % cases of duplicate tumours were located outside the irradiated areas. Four of the six newly formed lung tumours, three of the seven newly formed skin tumours, and seven tumours in the contralateral breast were identified in the irradiated areas. Latency time till the formation of duplicate tumours ranged from two to twelve years. The median of the latency time was seven years. Within five years after irradiation a total of 14 secondary tumours formed, i.e. 42 % of the total. Within ten years after irradiation most of the duplicate tumours formed. 17 duplicates were diagnosed in this category, i.e. 52 %. 52 %. In one type of cancer (3 %), brain tumour, and meninges, the latency time was 12 years. Furthermore, I calculated relative risk. The values of relative risk determined were greater than 1 for all types of tumours. The lowest value relative risk was observed in skin cancer, which was 1,939. On the other hand, the highest value of the relative risk was observed in endometrial neoplasm. The value of relative risk reached 48.78. Through this calculation of relative risks I confirmed the hypothesis that after irradiation of breast cancer there is an increasing number of duplicate tumours in comparison with the occurrence of tumours in the general population. Despite the increased values of relative risk, the benefits of radiotherapy in cancer treatment are irreplaceable. When using radio therapy, it is necessary to count with some risk of late complications.
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Development of the mammographic screening in the Czech Republic
KREJČÍ, Klára
Nowadays the most common cancer among women in the Czech Republic is represented by malignant tumour in breast. The nationwide mammographic screening programme was officially introduced in the Czech Republic in September 2002 and it is based on regular and preventive mammographic screening to women in order to detect early any neoplastic disease even in cases when women do not have any symptoms or difficulties. The main aim of the mammographic screening is to confirm or to disprove malignancy and if the malignancy is detected then to make sure that it is in the earliest stage. The thesis focuses on the development of the mammographic screening in the Czech Republic but it also pursue the number of mammographic screenings to number of recording of carcinoma no matter whether it is about the whole number of recorded carcinoma or the number of carcinoma in terms of mammographic screening and also in number of private patience. The first aim of the thesis was to find out which doctor often sends their patients to mammographic screening whether it is a general practitioner of a gynaecologist. These data were found out from the Mammographic screening Centre in Havlíčkův Brod. The second aim was to analyse the most frequent reason of patients, who requested the screening themselves. To collect the data it was done by a questionnaire method which answered sixty women. Thirty of them answered it in a clinic Medipoint Ltd and other thirty of them in the Mammographic screening Centre Havlíčkův Brod. The questionnaire was done by women younger than 40 years old who were tested for the ultrasound screening as by women over 40 years old who were tested for the mammographic screening. The information filled in this questionnaire included the date, the region they are from, age, and the reason why they came privately for the mammographic or ultraviolet screening. The hypothesis, that the number of mammographic screening requested by private patients is increasing, was confirmed due to the collected data from the Mammographic screening Centre in Havlíčkův Brod. As a result from the research we can see that since 2002, when the mammographic screening programme began nationwide, has been an enormous progress in the mammographic screening in the Czech Republic. Nowadays more women request to be tested for the mammographic screening in spite of the rising incidence of the cancer the mortality remains stable. This proves that this mammographic screening programme has a positive effect on the prevention of this illness.
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The risk of chronic lesions after radiation therapy in patients with breast cancer
KŘÍŽOVÁ, Jana
Breast carcinoma is the most common cancer in women. In 2009, 5,975 new cases were diagnosed in the Czech Republic. One of the main treatment modalities is radiotherapy, which, besides bringing treatment effects, may also cause post-radiation changes that significantly influence patients? quality of life. The work focuses on monitoring the occurrence of post-radiation changes following radiotherapy as part of breast carcinoma treatment ? chronic radiodermatitis, hypodermic fibrosis and lymphedema, all at Masaryk Memorial Cancer Institute Brno. After the end of radiotherapeutic treatment these changes are monitored by the physicians during regular checks and classified on the RTOG/EORTC scale. I used a set of 98 patients (97 women and 1 man) treated at the Masaryk Memorial Cancer Institute Brno between 1998 and 2009 who suffered from the mentioned post-radiation changes. The data was assessed upon the purpose, radiation equipment used for the radiotherapy, and the degree of the studied conditions. Occurrence of lymphedema prior to radiotherapy was statistically analysed as well. All the patients received the same dose of 50 Gy with a standard fractionation scheme of 25 fractions by 2 Gy, and therefore no evaluation of coincidence of the applied dose with the risk of chronic changes occurrence was possible. Consequent changes occurred in 74 % of the studied patients. Statistics shows that patients who received radiation treatment of mamma or chest and regional lymph nodes were at higher risk of suffering chronic changes to the skin and higher risk of lymphedema, but at lower risk of hypodermic fibrosis.
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